Superficial Collagen Fibril Modulus and Pericellular Fixed Charge Density Modulate Chondrocyte Volumetric Behaviour in Early Osteoarthritis

Abstract

The aim of this study was to investigate if the experimentally detected altered chondrocyte volumetric behavior in early osteoarthritis can be explained by changes in the extracellular and pericellular matrix properties of cartilage. Based on our own experimental tests and the literature, the structural and mechanical parameters for normal and osteoarthritic cartilage were implemented into a multiscale fibril-reinforced poroelastic swelling model. Model simulations were compared with experimentally observed cell volume changes in mechanically loaded cartilage, obtained from anterior cruciate ligament transected rabbit knees. We found that the cell volume increased by 7% in the osteoarthritic cartilage model following mechanical loading of the tissue. In contrast, the cell volume decreased by 4% in normal cartilage model. These findings were consistent with the experimental results. Increased local transversal tissue strain due to the reduced collagen fibril stiffness accompanied with the reduced fixed charge density of the pericellular matrix could increase the cell volume up to 12%. These findings suggest that the increase in the cell volume in mechanically loaded osteoarthritic cartilage is primarily explained by the reduction in the pericellular fixed charge density, while the superficial collagen fibril stiffness is suggested to contribute secondarily to the cell volume behavior.

A multi-scale finite element model for investigation of chondrocyte mechanics in normal and medial meniscectomy human knee joint during walking

“…The cell level model was driven by displacements and pore pressures obtained from the nodal outputs of the compartment level model. The cell level submodel was composed of a single chondrocyte (diameter¼10 mm) and a surrounding PCM (thickness ¼2.5 mm) (Guilak and Mow, 2000;Julkunen et al, 2009;Korhonen et al, 2011;Tanska et al, 2013). The chondrocyte and PCM were embedded into the surrounding ECM (Buckwalter and Mankin, 1997;Guilak and Mow, 2000;Guilak et al, 2005Guilak et al, , 1995Han et al, 2011;Julkunen et al, 2009;Korhonen et al, 2011;Tanska et al, 2013).…”

“…The cell center was located at $ 9.5% of the total cartilage thickness (from the surface). The cell included constant hyperelastic parameters and permeability (Julkunen et al, 2009;Tanska et al, 2013), but the fibrils were ignored. The PCM was modeled as an FRPVE material and it included circumferential collagen fibrils along with the cell surface (Kääb et al, 2003;Poole, 1997) as well as constant hyperelastic parameters and permeability for the non-fibrillar matrix (Tanska et al, 2013).…”

“…Cell level responses have been studied by applying multi-scale approaches (Guo et al, 2014;Halloran et al, 2012;Han et al, 2011; Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/jbiomech www. JBiomech.com et al, 2009;Korhonen et al, 2011;Moo et al, 2012;Sibole and Erdemir, 2012;Sibole et al, 2013;Tanska et al, 2013;Varadarajan et al, 2008). However, joint loading and/or constitutive equations for cartilage were relatively simple in these models (e.g., axial loading, isotropic elastic cartilage).…”

The Influence of Cell-Matrix Attachment and Matrix Development on the Micromechanical Environment of the Chondrocyte in Tissue-Engineered Cartilage

“…28 Besides these agreements, it is also worth mentioning that the constitutive material model for native ECM has previously been validated and used for studies at both the macroscopic tissue 21,22,30 and the microscopic cell level. 24,[31][32][33][34][35][36] The different macroscopic and microscopic depthdependent strain fields between native cartilage and TE constructs may have implications for the mechano-response of the chondrocytes to mechanical stimulation. Cells may have adapted over time to particular in vivo environments, which may or may not resemble those that are exposed to in TE constructs, depending on the location where they end up after seeding.…”

“…24 The chondrocyte was modeled as a homogeneous biphasic material with Young's modulus of 0.001 MPa, Poisson's ratio of 0.4, solid fraction of 0.17, and permeability of 1 · 10 -12 m 4 /N$s. 25,26 To study the influence of the gradual development of PCM during culture in TE constructs, the matrix content within PCM was varied from 0.25 to 0.5, 0.75, and 1.0 of that in the PCM in native cartilage.…”